Pyrrole derivatives

ABSTRACT

A pyrrole derivative having excellent anti-microbial activities is disclosed. This compound is represented by the following formula (I): ##STR1## wherein X 1  and X 2  are the same or different and mean individually a halogen atom, R 1  denotes an alkyl, cycloalkyl, haloalkyl, alkenyl, substituted or unsubstituted phenyl, substituted or unsubstituted aralkyl group or a group --COR 3  in which R 3  is an alkyl group having at least five carbon atoms or a cycloalkyl, haloalkyl, alkenyl, substituted or unsubstituted phenyl, substituted or unsubstituted aralkyl, or heterocyclic group, and R 2  stands for a hydrogen or halogen atom or an alkyl group, with a proviso that R 1  is other than a hydrogen atom or methyl group when X 1 , X 2  and R 2  are each a bromine atom.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to novel pyrrole derivatives, and more specifically to pyrrole derivatives which have excellent antimicrobial activities against bacteria, Trichophyton, pathogenic fungi for plants, etc. and are usable as pharmaceutical products, agricultural chemicals, antiseptics and the like.

2. Description of the Related Art

Pyrrolomycins have heretofore been known as pyrrole derivatives having antimicrobial activities against bacteria, Trichophyton, and pathogenic fungi for plants (Japanese Patent Application Laid-Open No. 126863/1983). Their effects are however still not fully satisfactory, resulting in a desire for the development of a compound having even better effects.

SUMMARY OF THE INVENTION

The present inventors have synthesized a variety of pyrrole derivatives and have investigated their antibacterial effects. As a result, it has been found that the pyrrole derivatives represented by the below-described formula (I) have excellent antimicrobial activities against bacteria, Trichophyton, pathogenic fungi for plants, etc., leading to completion of this invention.

This invention therefore provides a pyrrole derivative represented by the following formula (I): ##STR2## wherein X₁ and X₂ are the same or different and mean individually a halogen atom, R₁ denotes an alkyl, cycloalkyl, haloalkyl, alkenyl, substituted or unsubstituted phenyl, substituted or unsubstituted aralkyl group or a group --COR₃ in which R₃ is an alkyl group having at least five carbon atoms or a cycloalkyl, haloalkyl, alkenyl, substituted or unsubstituted phenyl, substituted or unsubstituted aralkyl, or heterocyclic group, and R₂ stands for a hydrogen or halogen atom or an alkyl group, with a proviso that R₁ is other than a hydrogen atom or methyl group when X₁, X₂ and R₂ are each a bromine atom.

The compounds (I) of this invention obtained as described above exhibit excellent antimicrobial activity against bacteria, Candida, Trichophyton and pathogenic fungi for plants, and are hence useful as pharmaceutical products, agricultural chemicals and antiseptics.

DETAILED DESCRIPTION OF THE INVENTION

The compound (I) of this invention can be prepared, for example, by any one of the following processes:

Process 1

A compound (Ia) is prepared by iodinating a pyrrole derivative (III) in accordance with the following formula: ##STR3## wherein X₁ and R₂ have the same meanings as defined above, and R'₁ denotes an alkyl, cycloalkyl, haloalkyl, alkenyl, substituted or unsubstituted phenyl or substituted or unsubstituted aralkyl group.

The above reaction can be conducted easily by reacting iodine with the pyrrole derivative (III) in the presence of sodium iodide or potassium iodide in a mixed solvent such as dioxane-water.

Examples of the combination of the starting compound (III) in this process and the compound (Ia) obtained by this process are given in Table 1.

                                      TABLE 1                                      __________________________________________________________________________     Starting compound (III)   Invention compound (Ia)                              __________________________________________________________________________     2-(2-Methoxybenzoyl)-4,5-dichloropyrrole                                                                 2-(2-Methoxybenzoyl)-3-iodo-4,5-dichloropyrrole                                8                                                    2-(2-n-Butoxybenzoyl)-4,5-dichloropyrrole                                                                2-(2-n-Butoxybenzoyl)-3-iodo-4,5-dichloropyrrole                               .                                                    2-(2-Octyloxybenzoyl)-4,5-dichloropyrrole                                                                2-(2-Octyloxybenzoyl)-3-iodo-4,5-dichloropyrrole                               7                                                    2-(2-Cyclopentyloxybenzoyl)-4,5-dichloropyrrole                                                          2-(2-Cyclopentyloxybenzoyl)-3-iodo-4,5-dichlorop                               yrrole                                               2-(2-Phenoxybenzoyl)-4,5-dichloropyrrole                                                                 2-(2-Phenoxybenzoyl)-3-iodo-4,5-dichloropyrrole                                N                                                    2-(2-Phenoxy-5-methylbenzoyl)-4,5-dichloropyrrole                                                        2-(2-Phenoxy-5-methylbenzoyl)-3-iodo-4,5-dichlor                               opyrrole                                             2-[2-(4-Methylphenoxy)benzoyl]-4,5-dichloropyrrole                                                       2-[2-(4-Methylphenoxy)benzoyl]-3-iodo-4,5-dichlo                               ropyrrole                                            2-[2-(2-Chloroethoxy)benzoyl]-4,5-dichloropyrrole                                                        2-[2-(2-Chloroethoxy)benzoyl]-3-iodo-4,5-dichlor                               opyrrole                                             2-(2-Allyloxybenzoyl)-4,5-dichloropyrrole                                                                2-(2-Allyloxybenzoyl)-3-iodo-4,5-dichloropyrrole     2-[2-(1-Propenyloxy)benzoyl]-4,5-dichloropyrrole                                                         2-[2-(1-Propenyloxy)benzoyl]-3-iodo-4,5-dichloro                               pyrrole                                              2-(2-Methoxy-5-fluorobenzoyl)-4,5-dichloropyrrole                                                        2-(2-Methoxy-5-fluorobenzoyl)-3-iodo-4,5-dichlor                               opyrrole                                             2-(2-Benzyloxybenzoyl)-4,5-dichloropyrrole                                                               2-(2-Benzyloxybenzoyl)-3-iodo-4,5-dichloropyrrol                               e                                                    2-[2-(4-Methoxybenzyloxy)benzoyl]-4,5-dichloropyrrole                                                    2-[2-(4-Methoxybenzyloxy)benzoyl]-3-iodo-4,5-dic                               hloropyrrole                                         __________________________________________________________________________

Process 2

A compound (Ib) is prepared by halogenating a pyrrole derivative (II') or (III') in accordance with the following scheme: ##STR4## wherein X₁ and X₂ have the same meanings as defined above, R'₂ denotes a halogen atom, and R'₁ stands for an alkyl, cycloalkyl or haloalkyl group.

According to this reaction, a halogenating agent is caused to act on the pyrrole derivative (II') in an inert solvent to obtain the compound (Ib) directly, or to conduct partial halogenation to obtain the pyrrole derivative (III'), followed by reaction with a different halogenating agent to obtain the compound (Ib).

As the halogenating agents, t-butylhypochlorite, bromine, chlorine or the like may be used.

Examples of the combination of the starting compound (II') in this process and the compound (Ib) obtained by this process are given in Table 2.

                                      TABLE 2                                      __________________________________________________________________________     Starting compound (II') Invention compound (Ib)                                __________________________________________________________________________     2-(2-Ethoxy-5-bromobenzoyl)pyrrole                                                                     2-(2-Ethoxy-5-bromobenzoyl)-3,4,5-tribromopyrrole                              N                                                      2-(2-Ethoxy-5-fluorobenzoyl)pyrrole                                                                    2-(2-Ethoxy-5-fluorobenzoyl)-3,4,5-tribromopyrrole                             O                                                      2-(2-Cyclopentyloxy-5-bromobenzoyl)pyrrole                                                             2-(2-Cyclopentyloxy-5-bromobenzoyl)-3,4,5-tribromo                             pyrrole                                                2-(2-Propoxy-5-chlorobenzoyl)pyrrole                                                                   2-(2-Propoxy-5-chlorobenzoyl)-3,4,5-trichloropyrro                             le                                                     2-(2-Butoxy-5-fluorobenzoyl)pyrrole                                                                    2-(2-Butoxy-5-fluorobenzoyl)-3-bromo-4,5-dichlorop                             yrrole                                                 2-(2-Butoxy-5-bromobenzoyl)pyrrole                                                                     2-(2-butoxy-5-bromobenzoyl)-3-bromo-4,5-dichloropy                             rrole                                                  2-(2-Cyclohexyloxy-5-bromobenzoyl)pyrrole                                                              2-(2-Cyclohexyloxy-5-bromobenzoyl)-3-bromo-                                    4,5-dichloropyrrole                                    2-(2-Cyclohexyloxy-5-chlorobenzoyl)pyrrole                                                             2-(2-Cyclohexyloxy-5-chlorobenzoyl)-3-bromo-                                   4,5-dichloropyrrole                                    2-(2-Hexyloxy-5-fluorobenzoyl)pyrrole                                                                  2-(2-Hexyloxy-5-fluorobenzoyl)-3,4,5-tribromopyrro                             le                                                     2-(2-Hexyloxy-5-bromobenzoyl)pyrrole                                                                   2-(2-Hexyloxy-5-bromobenzoyl)-3-bromo-4,5-dichloro                             pyrrole                                                2-(2-Nonyloxy-5-bromobenzoyl)pyrrole                                                                   2-(2-Nonyloxy-5-bromobenzoyl)-3,4,5-tribromopyrrol                             e                                                      2-[2-(2,2,2-trifluoroethoxy)-5-fluorobenzoyl]pyrrole                                                   2-[2-(2,2,2-trifluoroethoxy)-5-fluorobenzoyl]-                                 3,4,5-tribromopyrrole                                  2-[2-(3-Chloropropoxy)-5-bromobenzoyl]pyrrole                                                          2-[2-(3-chloropropoxy)-5-bromobenzoyl]-3-bromo-                                4,5-dichloropyrrole                                    __________________________________________________________________________

Process 3

A compound (Ic) is prepared by acylating a pyrrole derivative (IV) in accordance with the following formula: ##STR5## wherein X₁, X₂, R₂ and R₃ have the same meanings as defined above.

This reaction is conducted by reacting a conventional acylating agent, for example, an acid anhydride or acid halide with the compound (IV) in the presence of a base.

Examples of the combination of the starting compound (IV) and acylating agent in this process and the compound (Ic) obtained by this process are given in Table 3.

                                      TABLE 3                                      __________________________________________________________________________     Starting compound (IV)                                                                         Acylating agent                                                                              Invention compound (Ic)                          __________________________________________________________________________     2-(2-Hydroxybenzoyl)-                                                                          Enanthic anhydride                                                                           2-(2-Heptanoyloxybenzoyl)-3,4,5-tribromopyrr                                   ole                                              3,4,5-tribromopyrrole                                                          2-(2-Hydroxybenzoyl)-                                                                          Caprylic anhydride                                                                           2-(2-Octanoyloxybenzoyl)-3,4,5-tribromopyrro                                   le                                               3,4,5-tribromopyrrole                                                          2-(2-Hydroxybenzoyl)-                                                                          Pelargonic anhydride                                                                         2-(2-Nonanoyloxybenzoyl)-3,4,5-tribromopyrro                                   le                                               3,4,5-tribromopyrrole                                                          2-(2-Hydroxybenzoyl)-                                                                          Capric anhydride                                                                             2-(2-Decanoyloxybenzoyl)-3,4,5-tribromopyrro                                   le                                               3,4,5-tribromopyrrole                                                          2-(2-Hydroxybenzoyl)-                                                                          Undecanoic acid chloride                                                                     2-(2-Undecanoyloxybenzoyl)-3,4,5-tribromopyr                                   role                                             3,4,5-tribromopyrrole                                                          2-(2-Hydroxybenzoyl)-                                                                          Pentadecanoic acid chloride                                                                  2-(2-Pentadecanoyloxybenzoyl)-3,4,5-tribromo                                   pyrrole                                          3,4,5-tribromopyrrole                                                          2-(2-Hydroxybenzoyl)-                                                                          Cyclopentanecarboxylic                                                                       2-(2-Cyclopentanecarbonyloxybenzoyl)-            3,4,5-tribromopyrrole                                                                          acid chloride 3,4,5-tribromopyrrole                            2-(2-Hydroxybenzoyl)-                                                                          Cyclohexanecarboxylic                                                                        2-(2-Cyclohexanecarbonyloxybenzoyl)-             3,4,5-tribromopyrrole                                                                          acid chloride 3,4,5-tribromopyrrole                            2-(2-Hydroxybenzoyl)-                                                                          Chloroacetyl chloride                                                                        2-(2-Chloroacetyloxybenzoyl)-3,4,5-tribromop                                   yrrole                                           3,4,5-tribromopyrrole                                                          2-(2-Hydroxybenzoyl)-                                                                          3-Chloropropionic acid                                                                       2-(3-Chloropropionylbenzoyl)-                    3,4,5-tribromopyrrole                                                                          chloride      3,4,5-tribromopyrrole                            2-(2-Hydroxybenzoyl)-                                                                          Crotonic anhydride                                                                           2-(2-Crotonoyloxybenzoyl)-3,4,5-tribromopyrr                                   ole                                              3,4,5-tribromopyrrole                                                          2-(2-Hydroxybenzoyl)-                                                                          Benzoyl chloride                                                                             2-(2-Benzoyloxybenzoyl)-3,4,5-tribromopyrrol                                   e                                                3,4,5-tribromopyrrole                                                          2-(2-Hydroxybenzoyl)-                                                                          P-Methoxybenzoyl chloride                                                                    2-(2-p-Methoxybenzoylpxybenzoyl)-                3,4,5-tribromopyrrole         3,4,5-tribromopyrrole                            2-(2-Hydroxybenzoyl)-                                                                          3-Phenylpropionyl chloride                                                                   2-[2-(3-Phenylpropionyloxy)benzoyl]-             3,4,5-tribromopyrrole         3,4,5-tribromopyrrole                            2-(2-Hydroxybenzoyl)-                                                                          3-p-Methoxyphenylpropionyl                                                                   2-[2-(3-p-Methoxyphenylpropionyloxy)-            3,4,5-tribromopyrrole                                                                          chloride      3,4,5-tribromopyrrole                            2-(2-Hydroxybenzoyl)-3-                                                                        Enanthic anhydride                                                                           2-(2-heptanoyloxybenzoyl)-3-iodo-4,5-dichlor                                   opyrrole                                         iodo-4,5-dichloropyrrole                                                       2-(2-Hydroxybenzoyl)-3-                                                                        Caprylic anhydride                                                                           2-(2-Octanoyloxybenzoyl)-3-iodo-4,5-dichloro                                   pyrrole                                          iodo-4,5-dichloropyrrole                                                       2-(2-Hydroxybenzoyl)-3-                                                                        Pelargonic abhydride                                                                         2-(2-Nonanoyloxybenzoyl)-3-iodo-4,5-dichloro                                   pyrrole                                          iodo-4,5-dichloropyrrole                                                       2-(2-Hydroxybenzoyl)-3-                                                                        Capric anhydride                                                                             2-(2-Decanoyloxybenzoyl)-3-iodo-4,5-dichloro                                   pyrrole                                          iodo-4,5-dichloropyrrole                                                       2-(2-Hydroxybenzoyl)-3-                                                                        Undecanoic acid chloride                                                                     2-(2-Undecanoyloxybenzoyl)-3-iodo-               iodo-4,5-dichloropyrrole      4,5-dichloropyrrole                              2-(2-Hydroxybenzoyl)-3-                                                                        Pentadecanoic acid                                                                           2-(2-Pentadecanoyloxybenzoyl)-3-iodo-            iodo-4,5-dichloropyrrole                                                                       chloride      4,5-dichloropyrrole                              2-(2-Hydroxybenzoyl)-3-                                                                        Cyclopentanecarboxylic                                                                       2-(2-Cyclopentanecarbonyloxybenzoyl)-3-iodo-     iodo-4,5-dichloropyrrole                                                                       acid chloride 4,5-dichloropyrrole                              2-(2-Hydroxybenzoyl)-3-                                                                        Cyclohexanecarboxylic                                                                        2-(2-Cyclohexanecarbonyloxybenzoyl)-3-iodo-      iodo-4,5-dichloropyrrole                                                                       acid chloride 4,5-dichloropyrrole                              2-(2-Hydroxybenzoyl)-3-                                                                        Chloroacetyl chloride                                                                        2-(2-Chloroacetylaxybenzoyl)-3-iodo-             iodo-4,5-dichloropyrrole      4,5-dichloropyrrole                              2-(2-Hydroxybenzoyl)-3-                                                                        3-Chloropropionic acid                                                                       2-[2-(3-Chloropropionyloxy)benzoyl]-3-iodo-      iodo-4,5-dichloropyrrole                                                                       chloride      4,5-dichloropyrrole                              2-(2-Hydroxtbenzoyl)-3-                                                                        Crotonic anhydride                                                                           2-(2-Crotonoyloxybenzoyl)-3-iodo-4,5-dichlor                                   opyrrole                                         iodo-4,5-dichloropyrrole                                                       2-(2-Hydroxybenzoyl)-3-                                                                        Benzoyl chloride                                                                             2-(2-Benzoyloxybenzoyl)-3-iodo-4,5-dichlorop                                   yrrole                                           iodo-4,5-dichloropyrrole                                                       2-(2-Hydroxybenzoyl)-3-                                                                        p-Methoxybenzoyl chloride                                                                    2-(2-p-Methoxybenzoyloxybenzoyl)-3-iodo-         iodo-4,5-dichloropyrrole      4,5-dichloropyrrole                              2-(2-Hydroxybenzoyl)-3-                                                                        3-Phenylpropionyl                                                                            2-[2-(3-Phenylpropionyloxy)benzoyl]-3-iodo-      iodo-4,5-dichloropyrrole                                                                       chloride      4,5-dichloropyrrole                              2-(2-Hydroxybenzoyl)-3-                                                                        3-p-Methoxyphenyl-                                                                           2-[2-(3-p-Methoxyphenylpropionyloxy)benzoyl]                                   -3-                                              iodo-4,5-dichloropyrrole                                                                       propionyl chloride                                                                           iodo-4,5-dichloropyrrole                         2-(2-Hydroxy-5-fluoro-                                                                         Enanthic anhydride                                                                           2-(2-Heptanoyloxy-5-fluorobenzoyl)-              benzoyl)-3,4,5-               3,4,5-tribromopyrrole                            tribromopyrrole                                                                2-(2-Hydroxy-5-fluoro-                                                                         Pelargonic anhydride                                                                         2-(2-Nananoyloxy-5-fluorobenzoyl)-               benzoyl)-3,4,5-               3,4,5-tribromopyrrole                            tribromopyrrole                                                                2-(2-Hydroxy-5-fluoro-                                                                         Myristic acid chloride                                                                       2-(2-Myristynoyloxy-5-fluorobenzoyl)-            benzoyl)-3,4,5-               3,4,5-tribromopyrrole                            tribromopyrrole                                                                2-(2-Hydroxy-5-fluoro-                                                                         Cyclopentanecarboxylic                                                                       2-(2-Cyclopenanecarbonyloxy-5-fluorobenzoyl)                                   -                                                benzoyl)-3,4,5- acid chloride 3,4,5-tribromopyrrole                            tribromopyrrole                                                                2-(2-Hydroxy-5-fluoro-                                                                         3-Chloropropionic                                                                            2-[2-(3-Chloropropionyloxy)-5-fluorobenzoyl]                                   -                                                benzoyl)-3,4,5- acid chloride 3,4,5-tribromopyrrole                            tribromopyrrole                                                                2-(2-Hydroxy-5-fluoro-                                                                         Crotonic anhydride                                                                           2-(2-Crotonyloxy-5-fluorobenzoyl)-               benzoyl)-3,4,5-               3,4,5-tribromopyrrole                            tribromopyrrole                                                                2-(2-Hydroxy-5-fluoro-                                                                         Benzoyl chloride                                                                             2-(2-Benzoyloxy-5-fluorobenzoyl)-                benzoyl)-3,4,5-               3,4,5-tribromopyrrole                            tribromopyrrole                                                                2-(2-Hydroxy-5-fluorobenzoyl)-                                                                 p-Toluoyl chloride                                                                           2-(2-p-Toluoyloxy-5-fluorobenzoyl)-              3,4,5-tribromopyrrole         3,4,5-tribromopyrrole                            2-(2-Hydroxy-5-fluorobenzoyl)-                                                                 2-Phenylpropionyl                                                                            2-[2-(3-Phenylpropionyloxy)-5-fluorobenzoyl]                                   -                                                3,4,5-tribromopyrrole                                                                          chloride      3,4,5-tribromopyrrole                            2-(2-Hydroxy-5-methylbenzoyl)-                                                                 Enanthic anhydride                                                                           2-(2-Heptanoyloxy-5-methylbenzoyl)-              3,4-5-tribromopyrrole                                                          2-(2-Hydroxy-5-methylbanzoyl)-                                                                 Pelargonic anhydride                                                                         2-(2-Nonanoyloxy-5-methylbenzoyl)-               3,4-5-tribromopyrrole         3,4,5-tribromopyrrole                            2-(2-Hydroxy-5-methylbenzoyl)-                                                                 Cyclopropanecarboxylic                                                                       2-(2-Cyclopropanecarbonyloxy-5-methylbanzoyl                                   )-                                               3,4-5-tribromopyrrole                                                                          acid chloride 3,4,5-tribromopyrrole                            2-(2-Hydroxy-5-methylbenzoyl)-                                                                 Crotonic anhydride                                                                           2-(2-Crotonyloxy-5-methylbenzoyl)-               3,4-5-tribromopyrrole         3,4,5-tribromopyrrole                            2-(2-Hydroxy-5-methylbenzoyl)-                                                                 Benzoyl chloride                                                                             2-(2-Benzoyloxy-5-methylbenzoyl)-                3,4-5-tribromopyrrole         3,4,5-tribromopyrrole                            2-(2-Hydroxy-5-methylbenzoyl)-                                                                 3-Phenylpropionyl                                                                            2-[2-(3-Phenylpropionyloxy)-5-methylbenzoyl)                                   -                                                3,4-5-tribromopyrrole                                                                          chloride      3,4,5-tribromopyrrole                            2-(2-Hydroxybenzoyl)-3,4,5-                                                                    2-Furoyl chloride                                                                            2-[2-(2-furoyloxy)benzoyl]-3,4,5-tribromopyr                                   role                                             tribromopyrrole (Furancarboxylic acid                                                          chloride)                                                      2-(2-Hydroxybenzoyl)-3-iodo-                                                                   2-Furanoyl chloride                                                                          2-[2-(2-furoyloxy)benzoyl]-3-iodo-               4,5-dichloropyrrole                                                                            (Furancarboxylic acid                                                                        4,5-dichloropyrrole                                              chloride)                                                      2-(2-Hydroxy-5-fluorobenzoyl)-                                                                 2-Furoyl chloride                                                                            2-[2-(2-furoyloxy)-5-fluorobenzoyl]-             3,4,5-tribrmompyrrole         3,4,5-tribromopyrrole                            2-(2-Hydroxy-5-methylbenzoyl)-                                                                 2-Furoyl chloride                                                                            2-[2-(2-furoyloxy)-5-methylbenzoyl]-             3,4,5-tribromopyrrole         3,4,5-tribromopyrrole                            2-(2-Hydroxybenzoyl)-3,4,5-                                                                    2-Thienoyl chloride                                                                          2-[2-(2-Thienoyloxy)benzoyl]-                    tribromopyrrole (Thiophenecarboxylic                                                                         3,4,5-tribromopyrrole                                            acid chloride)                                                 2-(2-Hydroxybenzoyl)-3-iodo-                                                                   2-Thienoyl chloride                                                                          2-[2-(2-Thienoyloxy)benzoyl]-3-iodo-             4,5-dichloropyrrole                                                                            (Thiophenecarboxylic                                                                         4,5-dichloropyrrole                                              acid chloride)                                                 2-(2-Hydroxy-5-fluorobenzoyl)-                                                                 2-Thienoyl chloride                                                                          2-[2-(2-Thienoyloxy)-5-fluorobenzoyl]-           3,4,5-tribromopyrrole                                                                          (Thiophenecarboxylic                                                                         3,4,5-tribromopyrrole                                            acid chloride)                                                 2-(2-Hydroxy-5-methylbenzoyl)-                                                                 2-Thienoyl chloride                                                                          2-[2-(2-Thienoyloxy)-5-methylbenzoyl]-           3,4,5-tribromopyrrole                                                                          )Thiophenecarboxylic                                                                         3,4,5-tribromopyrrole                                            acid chloride)                                                 2-(2-Hydroxybenzoyl)-3,4,5-                                                                    Nicotinoyl chloride                                                                          2-(2-Nicotinoyloxybenzoyl)-3,4,5-tribromopyr                                   role                                             tribromopyrrole                                                                2-(2-Hydroxybenzoyl)-3-iodo-                                                                   Nicotinoyl chloride                                                                          2-(2-Nicotinoyloxybenzoyl)-3-iodo-               4,5-dichloropyrrole           4,5-dichloropyrrole                              2-(2-Hydroxy-5-fluorobenzoyl)-                                                                 Nicotinoyl chloride                                                                          2-(2-Nicotinoyloxy-5-fluorobenzoyl)-             3,4,5-tribromopyrrole         3,4,5-tribromopyrrole                            2-(2-Hydroxy-5-methylbenzoyl)-                                                                 Nicotinoyl chloride                                                                          2-(2-Nicotinoyloxy-5-methylbenzoyl)-             3,4,5-tribromopyrrole         3,4,5-tribromopyrrole                            __________________________________________________________________________

Incidentally, each pyrrole derivative (II) as a starting material for Process 2 can be prepared, for example, in accordance with any one of the following reaction formulae: (1) Pyrrole and a benzoic acid halide derivative (V) are reacted in the presence of a Lewis acid (for example, aluminum chloride) in an inert solvent. ##STR6## (2) To a pyrryl magnesium halide (VI) obtained by reacting a Grignard reagent with pyrrole, an alkyl benzoate derivative (VII) is reacted in an inert solvent. ##STR7## (3) To the compound (VI), a 2-pyridylthiobenzoate derivative (VIII)is reacted in the presence of CuI in an inert solvent. ##STR8##

Further, the pyrrole derivative (III), the starting material for Process 1, can be prepared by halogenating the pyrrole derivative (II).

(II)→(III)

This reaction can be carried out by reacting the pyrrole derivative (II) with a halogenating agent such as sulfuryl chloride in a suitable solvent.

On the other hand, the pyrrole derivative (IV) which is the starting material for Process 3 can be prepared, for example, by subjecting an ester-type derivative (IX) to the Fries rearrangement in accordance with the following formula: ##STR9##

This reaction may be conducted in a manner known per se in the art, for example, at a reaction temperature of 100-200° C. in the presence of a Lewis acid such as aluminum chloride, zinc chloride or tin tetrachloride in an inert solvent, such as carbon disulfide, sulfolane or nitrobenzene.

After the completion of the reaction, the thus-obtained compound (I) of this invention can be purified further by distilling off the solvent and recrystallizing it by a conventional method or if necessary, subjecting it to chromatography or the like.

The compound (I) of this invention can be converted into a pharmaceutically- and/or agriculturally-acceptable inorganic acid salt, organic acid salt or acid addition salt as needed. Examples of the inorganic salt may include the sodium salt, potassium salt, etc.

This invention will hereinafter be described by the following examples.

EXAMPLE 1

Added to 1.08 g of 2-(2-methoxybenzoyl)-4,5-dichloropyrrole were 16 ml of a 1:1 mixture of dioxane and water and 4 ml of a 1 N aqueous solution of sodium hydroxide to dissolve the pyrrole derivative, followed by the addition of 12 ml of an aqueous solution containing 1.2 g of iodine and 1.44 g of sodium iodide. The resultant mixture was stirred at room temperature for 15 hours. Thereafter, 40 ml of a 1 N aqueous solution of sodium thiosulfate was added, followed by stirring for 1 hour. Crystals thus deposited were collected by filtration, washed with water and then dried to obtain 1.24 g of 2-(2-methoxybenzoyl)-3-iodo-4,5-dichloropyrrole (Compound No. 1).

EXAMPLE 2

Dissolved in 5 ml of pyridine was 0.63 g of 2-(2-hydroxybenzoyl)-3,4,5-tribromopyrrole, followed by the addition of 1.5 ml of enanthic anhydride. The resultant mixture was stirred at room temperature for 24 hours. The reaction mixture was poured into 20 ml of ice water, followed by extraction with ether. The extract was washed successively with 1 N hydrochloric acid, a 2% aqueous solution of sodium hydrogen-carbonate, and water. The solution thus washed was dried over anhydrous sodium sulfate and then dried to solid under reduced pressure.

The residue was subjected to chromatography on a silica gel column, and from chloroform eluate fractions, 0.25 g of 2-(2-heptanoyloxybenzoyl)-3,4,5-tribromopyrrole (Compound No. 3) was obtained.

EXAMPLE 3

Compound No. 2 and the compounds numbered 4 ff. shown in Table 4 were obtained in a similar manner as in either one of Examples 1 and 2. Further, physical properties of Compounds 1 and 3 are also shown in the same table.

                                      TABLE 4                                      __________________________________________________________________________      ##STR10##                                           (I)                       Compound                                                                             In formula (I) Appearance                                                No.   X.sub.1                                                                          X.sub.2                                                                          R.sub.1 R.sub.2                                                                           Melting point (°C.)                                                               IR ν.sub.max.sup.KBr cm.sup.-1                                                       .sup.1 H-NMR δ ppm                                                       (CDCl.sub.3)                           __________________________________________________________________________     1     Cl                                                                               I CH.sub.3                                                                               H  Colorless crystals                                                                       3230     10.20(br,1H), 7.60-6.91(m,4H),                              174-175   1620     3.78(s,3H).                            2     Br                                                                               Br                                                                               CH.sub.3 (CH.sub.2).sub.5 CO                                                           F  Colorless crystals                                                                       3220     9.75(br,1H), 7.30-7.08(m,3H),                               68-72     1760     2.35(t,2H), 1.80-1.05(m,8H),                                          1620     0.86(t,3H).                            3     Br                                                                               Br                                                                               CH.sub.3 (CH.sub.2).sub.5 CO                                                           H  Colorless crystals                                                                       3220     9.90(br,1H), 7.65-7.14(m,4H),                               43-47     1760     2.35(t,2H), 1.82-1.00(m,8H),                                          1620     0.86(t,3H).                            4     Br                                                                               Br                                                                               CH.sub.3 (CH.sub.2).sub.8 CO                                                           H  Colorless crystals                                                                       3220     9.60(br,1H), 7.70-7.10(m,4H),                               71-73     1760     2.38(t,2H), 1.78-1.05(m,14H),                                         1620     0.86(t,3H).                            5     Br                                                                               Br                                                                               C.sub.6 H.sub.5 CO                                                                     H  Colorless crystals                                                                       3225     9.75(br.1H), 8.08-7.87(m,2H),                               161-163   1730     7.70-7.20(m,7H).                                                      1610                                            6     Cl                                                                               I CH.sub.3 (CH.sub.2).sub.5 CO                                                           H  Colorless crystals                                                                       3220     10.12(br,1H), 7.68-7.16(m,4H),                              70-72     1760     2.21(t,2H), 1.76-1.08(m,8H),                                          1620     0.90(t,3H).                            7     Cl                                                                               I CH.sub.3 (CH.sub.2).sub.8 CO                                                           H  Colorless crystals                                                                       3220     10.00(br,1H), 7.68-7.18(m,4H),                              50-58     1760     2.40(t,2H), 1.76-1.08(m,14H),                                         1620     0.89(t,3H).                            8     Cl                                                                               I C.sub.6 H.sub.5 CO                                                                     H  Colorless crystals                                                                       3230     9.78(br.1H), 7.96(d.d,2H),                                  145-147   1730     7.72-7.16(m,7H).                                                      1615                                            9     Cl                                                                               I Cl(CH.sub.2).sub.2 CO                                                                  H  Colorless syrup                                                                          3220     10.08(br.1H), 7.67-7.19(m,4H),                                        1750(neat)                                                                              3.72(t,2H), 2.88(t,2H).                                               1620                                            10    Br                                                                               Br                                                                               CH.sub.3 (CH.sub.2).sub.8 CO                                                           F  Colorless crystals                                                                       3220     10.00(br,1H), 7.30-7.00(m,3H),                              89-92     1750     2.38(t,2H), 1.80-1.05(m,14H),                                         1620     0.88(t,3H).                            11    Br                                                                               Br                                                                               C.sub.6 H.sub.5 CO                                                                     F  Colorless crystals                                                                       3250     9.67(br.1H), 7.96(m,2H),                                    180-181   1730     7.70-7.10(m,6H).                                                      1615                                            12    Br                                                                               Br                                                                               C.sub.6 H.sub.5 CO                                                                     CH.sub.3                                                                          Colorless crystals                                                                       3200     9.78(br.1H), 7.96(m,2H),                                    168-169   1745     7.70-7.10(m,6H), 2.41(s,3H).                                          1615                                            __________________________________________________________________________

TEST

With respect to some representative compounds of this invention, their microbial activities were investigated. The results are summarized in Table 5. Pyrrolomycin F₁ disclosed in Japanese Patent Application Laid-Open No. 126863/1983 was used as a comparative compound. In Table 5, the compound numbers indicate the same compounds as designated by their corresponding numbers in the above examples.

                                      TABLE 5                                      __________________________________________________________________________                       Minimum inhibitory concentration (MIC; μg/ml)                               Test Compound                                                Test microorganism                                                                               Compound 2                                                                            Compound 6                                                                            Compound 9                                                                            Pyrrolomycin F.sub.1                    __________________________________________________________________________     Bacillus subtilis ATCC 6633                                                                      <0.2    0.39  <0.2   <0.2                                    Staphylococcus aureus FDA 209P                                                                   <0.2    0.39  <0.2   <0.2                                    Candida albicans NHL 4019                                                                        12.5   12.5    6.25  >100                                    Candida albicans Yu-1200                                                                         12.5   12.5     6.25 >100                                    Saccharomyces cerevisiae ATCC 9763                                                               12.5   12.5    12.5  >100                                    Helminthosporium sesamum IAM 5012                                                                 6.25   6.25   6.25   6.25                                   Piricularia oryzae IAM 5016                                                                      <0.2   <0.2   <0.2   <0.2                                    Debaryomyces kloeckeri IFO 0015                                                                  12.5   12.5    12.5  >100                                    __________________________________________________________________________ 

We claim:
 1. A pyrrole derivative represented by the following formula (I): ##STR11## wherein X₁ and X₂ are the same or different and mean individually a halogen atom, R₁ denotes C₅ or C₆ cycloalkyl, halo-lower alkyl, lower alkenyl, lower-alkyl-substituted or unsubstituted phenyl, lower-alkoxyl substituted or unsubstituted benzyl group or a group --COR₃ in which R₃ is an alkyl group having at least five carbon atoms or a cyclo-C₃₋₆ alkyl, halo-lower alkyl, lower alkenyl, lower-alkyl- or lower-alkoxyl-substituted or unsubstituted phenyl, or lower-alkoxyl substituted or unsubstituted phenyl-lower alkyl, and R₂ stands for a hydrogen or halogen atom or a lower alkyl group. 